Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry

Arch Biochem Biophys. 2015 Jul;577-578:35-48. doi: 10.1016/j.abb.2015.04.009. Epub 2015 Apr 30.

Abstract

Relationship between structural diversity and biological activities of flavonoids has remained an important discourse in the mainstream of flavonoid research. In the current study anti-angiogenic, cytotoxic, antioxidant and cyclooxygenase (COX) inhibitory activities of diverse class of flavonoids including hydroxyl and methoxy substituted flavones, flavonones and flavonols have been evaluated in the light of developing flavonoids as a potential scaffold for designing novel anti-antiangiogenic agents. We demonstrate anti-angiogenic potential of flavonoids using in vivo chorioallantoic membrane model (CAM) and further elaborate the possible structural reasoning behind observed anti-angiogenic effect using in silico methods. Additionally, we report antioxidant potential and kinetics of free radical scavenging activity using DPPH and SOR scavenging assays. Current study indicates that selected flavonoids possess considerable COX inhibition potential. Furthermore, we describe cytotoxicity of flavonoids against selected cancer cell lines using MTT cell viability assay. Structural analysis of in silico docking poses and predicted binding free energy values are not only in accordance with the experimental anti-angiogenic CAM values from this study but also are in agreement with the previously reported literature on crystallographic data concerning EGFR and VEGFR inhibition.

Keywords: Anti-angiogenesis; Antioxidant; Cyclooxygenase inhibition; Cytotoxicity; Flavonoids; Molecular docking; VEGFR and EGFR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Antioxidants / chemistry*
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chickens
  • Cyclooxygenase Inhibitors / chemistry*
  • Cyclooxygenase Inhibitors / pharmacology
  • Drug Design*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Antioxidants
  • Cyclooxygenase Inhibitors
  • Flavonoids
  • ErbB Receptors
  • Receptors, Vascular Endothelial Growth Factor